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Sci Rep. 2016 Jun 15;6:27907. doi: 10.1038/srep27907.

Human Food Safety Implications of Variation in Food Animal Drug Metabolism.

Author information

1
Institute of Computational Comparative Medicine (ICCM), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
2
Department of Statistics, College of Arts and Sciences, Kansas State University, Manhattan, KS 66506, USA.

Abstract

Violative drug residues in animal-derived foods are a global food safety concern. The use of a fixed main metabolite to parent drug (M/D) ratio determined in healthy animals to establish drug tolerances and withdrawal times in diseased animals results in frequent residue violations in food-producing animals. We created a general physiologically based pharmacokinetic model for representative drugs (ceftiofur, enrofloxacin, flunixin, and sulfamethazine) in cattle and swine based on extensive published literature. Simulation results showed that the M/D ratio was not a fixed value, but a time-dependent range. Disease changed M/D ratios substantially and extended withdrawal times; these effects exhibited drug- and species-specificity. These results challenge the interpretation of violative residues based on the use of the M/D ratio to establish tolerances for metabolized drugs.

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